The Genetics of Eating Disorders
Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of eating behaviour and disturbances in attitudes and perceptions toward weight and shape. In AN, there is an extreme fear of weight gain despite increasing emaciation. BN usually emerges after a period of dieting (Bulik et al., 1997; Mussell et al., 1997) and is characterized by alternating patterns of binge eating and compensatory behaviour. Binge eating, which is the consumption of a large amount of food in an uncontrollable manner, is typically followed by either self-induced vomiting, excessive exercise, fasting, and/or the misuse of laxatives, diuretics or enemas. Although abnormally low body weight excludes a BN diagnosis, 25% to 30% of patients with BN have a prior history of AN (Eckert et al., 1995; Bulik et al., 1997; Strober, Freeman and Morrell, 1997; Garfinkel, Moldofsky and Garner, 1980). Common to individuals with AN and BN are pathological concern with weight and shape, depression, and anxiety (Mitchell et al., 1986; Keck et al., 1990; Fornari et al., 1992; Bulik et al., in press).
The aetiology of these disorders is presumed to be multiply influenced by developmental, social, and biological processes (Garner, 1993; Treasure and Campbell, 1994). However, the exact nature of these interactive processes remains incompletely understood. Cultural attitudes towards thinness have relevance to the psychopathology of eating disorders, but they are unlikely to be sufficient to account for the pathogenesis of these disorders. Notably, dieting behaviour is quite common in industrialized countries throughout the world, yet AN and BN affect only an estimated 0.3% to 0.7%, and 1.7% to 2.5%, respectively, of females in the general population (APA, 1994). Moreover, numerous descriptions of AN date from the middle of the 19th century suggesting that factors other than modern culture play an aetiologic role. In addition, both syndromes have a relatively homogeneous clinical presentation, sex distribution, and age-of-onset, supporting the possibility of some biological susceptibility. This is not to discount the role of culture, as the introduction of Western ideals of thinness may serve to release a biological propensity toward eating disorders (Becker, 1999) possibly by increasing behaviours such as dieting that may trigger the spiral of disordered eating.
Recent findings from behaviour genetic studies suggest that this biological vulnerability might be genetic in nature. In this paper, we will highlight these emerging findings and suggest areas for future research.
Family studies provide initial data regarding genetic influence on a disorder by establishing whether it clusters amongst biologically-related individuals. Controlled family studies have generally found increased rates of eating disorders in relatives of women with AN and BN compared to relatives of controls (Biederman et al., 1985; Lilenfeld et al., 1998; Strober et al., 1990, 2000). Findings from the largest and most systematic studies (Lilenfeld et al., 1998; Strober et al., 2000) suggest a 7–12-fold increase in the prevalence of AN and BN in relatives of eating disordered probands. This clustering of eating disorders in families of AN and BN individuals provides strong support for familial transmission of both disorders. However, given that first-degree relatives share both genes and environments, these studies cannot differentiate genetic versus environmental causes for the observed familiality. Systematic studies of twins are the means by which to disentangle the relative aetiological influence of genes and environment.
Twin studies differentiate genetic from environmental effects by comparing similarity for a trait/disorder between identical (monozygotic (MZ)) and fraternal twins (dizygotic (DZ)). This comparison is based on the fact that MZ twins share all of their genes identical by descent, whereas DZ twins share, on average, half of their genes identical by descent. Consequently, MZ twin correlations that are ≃ two times greater than DZ twin correlations suggest genetic effects. In general, greater MZ relative to DZ twin similarity for AN and BN has generally been found (Holland et al., 1984, 1988; Fichter and Noegel, 1990; Treasure and Holland, 1990). Estimates indicate that roughly 58–76% of the variance in the liability to AN (Klump et al., 2001; Wade et al., 2000), and 54–83% of the variance in the liability to BN (Bulik, Sullivan and Kendler, 1998; Kendler et al., 1991) can be accounted for by genetic factors. Although the confidence intervals on these estimates are wide, consistent findings across studies support moderate heritability of these traits (Bulik et al., 2000). For both AN and BN, the remaining variance in liability appears to be due to unique environmental factors (i.e., factors that are unique to siblings in the same family) rather than shared or common environmental factors (i.e., factors that are shared by siblings in the same family).
Eating disorder symptoms themselves also appear to be moderately heritable. Twin studies of binge eating, self-induced vomiting, and dietary restraint suggest that these behaviours are roughly 46–72% heritable (Sullivan, Bulik and Kendler, 1998; Klump et al., 2000). Likewise, pathological attitudes such as body dissatisfaction, eating and weight concerns, and weight preoccupation show heritabilities of roughly 32–72% (Klump et al., 2000; Rutherford et al., 1993; Wade et al., 1998, 1999). Taken together, findings suggest a significant genetic component to AN and BN as well as the attitudes and behaviours that contribute to, and correlate with, clinical eating pathology.